1-Heptanol, 2-propyl-, 1,1'-carbonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Additional information

As reported in literature (Mangelsdorf et al., 2003; Ulbrich and Palmer, 1995; Janer et al., 2007; Dent, 2007; Sanbuissho et al., 2009), histopathological examinations of reproductive tissues in repeated dose toxicity studies on rodents are of high value and high sensitivity for evaluation of reproductive toxicity in males and females. Thus, the available 90d study that included comprehensive examinations of reproduction tissues and parameters indicate that the substnce is not toxic to reproduction. The information above, the toxicokinetic profiles, as well as the lack of concern obtained from other toxicological endpoints, support the conclusion that Dipropylheptylcarbonate is not toxic to reproduction.

Dent MP. 2007. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.Regul Toxicol Pharmacol.2007 Aug; 48(3):241-58. Epub 2007 Apr 12.

Janer G, Hakkert BC, Slob W, Vermeire T, Piersma AH. 2007.A retrospective analysis of the two-generation study: What is the added value of the second generation? Reprod Toxicol 24:97-102.

Mangelsdorf, I., Buschmann, J., Orthen, B., 2003.Some aspects relating to the evaluation of the effects of chemicals on male fertility. Regulatory Toxicology and Pharmacology 37, 356–369

Sanbuissho A, Yoshida M, Hisada S,et al., 2009. Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats. J Toxicol Sci 2009.:SP1-22.

Ulbrich, B. and Palmer, A.K. (1995). Detection of effects on male reproduction: a literature survey. J. Am. College of Toxicology 14, 293–327

Justification for selection of Effect on fertility via oral route:
OECD and GLP compliant study with additional parameters to evaluate a potential toxicity to reproduction.

Effects on developmental toxicity

Description of key information

In a prenatal developmental toxicity study (OECD 414) in which rats were exposed up to 1000 mg/kg bw/day by oral gavage, the NOAEL for maternal toxicity was determined to be 300 mg/kg bw/day, and the NOAEL for prenatal developmental toxicity was established at 1000 mg/kg bw/day (the highest dose tested).  

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

Dipropylheptylcarbonate was tested for its prenatal developmental toxicity in Wistar rats. The test substance was administered as an oily solution to groups of 25 timemated female Wistar rats by gavage at doses of 100, 300, and 1000 mg/kg body weight/day (mg/kg bw/d) on gestation days (GD) 6 through 19. The control group, consisting of 25 females, was dosed with the vehicle (corn oil) in parallel. A standard dose volume of 4 mL/kg body weight was used for each test group. At terminal sacrifice on GD 20, 24-25 females per group had implantation sites.

Food consumption and body weights of the animals were recorded regularly throughout the study period. The state of health of the animals was checked each day. On GD 20, all females were sacrificed by cervical dislocation (under isoflurane anesthesia) and assessed by gross pathology, including weight determinations of the unopened uterus and the placentas. For each dam, corpora lutea were counted and number and distribution of implantation sites (differentiated between resorptions, live and dead fetuses) were determined. The fetuses were removed from the uterus, sexed, weighed and further investigated for external findings. Thereafter, one half of the fetuses of each litter were examined for soft tissue findings and the remaining fetuses for skeletal (inclusive cartilage) findings.

The following test substance-related, adverse effects/findings were noted:

Test group 3 (1000 mg/kg bw/d):

Dams

• Slightly reduced food consumption from GD 6-20, attaining statistical significance on

GD 15-17; if calculated for GD 6-19 4% less food consumption.

• Statistically significantly reduced mean body weight gain on GD 6-10 (30% below control)

and GD 15-17 (17% below).

• Statistically significantly reduced corrected body weight gain (12% below control).

• No test substance-related adverse effects on gestational parameters

Fetuses

• No test substance-related adverse findings

Test group 2 (300 mg/kg bw/d):

• No test substance-related adverse effects on dams, gestational parameters or fetuses

Test group 1 (100 mg/kg bw/d):

• No test substance-related adverse effects on dams, gestational parameters or fetuses

In conclusion, the no observed adverse effect level (NOAEL) for maternal toxicity is 300 mg/kg body weight/day based on the decreased food consumption and decreased body weight parameters in animals treated with 1000 mg/kg body weight/day Dipropylheptylcarbonate. The no observed adverse effect level (NOAEL) for prenatal developmental toxicity is 1000 mg/kg body weight/day. No adverse fetal findings of toxicological relevance were evident at any dose.

Justification for selection of Effect on developmental toxicity: via oral route:
OECD and GLP compliant study with additional parameters to evaluate a potential toxicity to reproduction.